Therapeutic melanoma inhibition by local micelle-mediated cyclic nucleotide repression.

The acidic tumor microenvironment in melanoma drives immune evasion by up-regulating cyclic adenosine monophosphate (cAMP) in tumor-infiltrating monocytes. Here we show that the release of non-toxic concentrations of an adenylate cyclase (AC) inhibitor from poly(sarcosine)-block-poly(L-glutamic acid γ-benzyl ester) (polypept(o)id) copolymer micelles restores antitumor immunity. In combination with selective, non-therapeutic regulatory T cell depletion, AC inhibitor micelles achieve a complete remission of established B16-F10-OVA tumors. Single-cell sequencing of melanoma-infiltrating immune cells shows that AC inhibitor micelles reduce the number of anti-inflammatory myeloid cells and checkpoint receptor expression on T cells. AC inhibitor micelles thus represent an immunotherapeutic measure to counteract melanoma immune escape. © 2021. The Author(s).

Citation

Kerstin Johann, Toszka Bohn, Fatemeh Shahneh, Natascha Luther, Alexander Birke, Henriette Jaurich, Mark Helm, Matthias Klein, Verena K Raker, Tobias Bopp, Matthias Barz, Christian Becker. Therapeutic melanoma inhibition by local micelle-mediated cyclic nucleotide repression. Nature communications. 2021 Oct 13;12(1):5981

PMID: 34645812

search → result